Project Summary The current proposal seeks to clarify the mechanisms underlying observed associations between alcohol and drug use disorders (AUD and DUD, respectively; SUD collectively) and suicidal behaviors (SB), including suicide attempts and completions. The research team has an extensive history of productive collaborations, including, in particular, psychiatric and substance use disorder research. We have access to Swedish national registries including medical, criminal, census, family, and socioeconomic data for nearly 11 million individuals; these resources will be linked to create detailed datasets encompassing a wide range of risk factors at personal, familial, and environmental levels. We will utilize these resources to extend our prior research through our pursuit of four specific aims. The first aim is to clarify the extent to which AUD/DUD is related to risk of suicidal behavior, accounting for critical confounding factors such as psychiatric comorbidity. Using genetic epidemiologic methods in conjunction with other informative designs aimed at facilitating causal inference, we will address whether the observed association is attributable to confounders, causal processes, or both. Second, we will examine how familial AUD, DUD, and SB impact individual risk, disentangling genetic from environmental components of risk through novel study designs developed through our ongoing collaboration. Parallel analyses will examine the role of exposure to AUD, DUD, and SB in the non-familial environment. Third, we will dissect health care utilization among those with AUD/DUD to identify potential SB risk indicators, with two primary foci: i) timing of and reason for doctor visits, and ii) associations between psychiatric/SUD medication usage and outcomes. Finally, we will incorporate our findings from the first three specific aims into integrative etiologic models of risk, separately for suicide attempts and completions. These models will be structured in a developmentally informative manner and enable us to identify mediational processes among risk factors for both outcomes. Critically, Sweden and the US have highly comparable rates of suicidal behavior and share many characteristics, including an ethnically and socioeconomically diverse population; however, the US lacks registry resources comparable to those available in Sweden. We expect that the statistical power of these registries, in conjunction with the research team's extensive expertise in psychiatric and substance abuse research, social and genetic epidemiology, and causal modeling, will yield substantive findings on the relationship between AUD/DUD and SB, with important implications for improving our efforts at SB prevention and intervention.